Are statin trials in diabetes representative of real-world diabetes care: a population-based study on statin initiators in Finland

Abstract

ObjectiveTo assess the representativeness of the Heart Protection Study (HPS) and the Collaborative Atorvastatin Diabetes Study (CARDS) for incident statin users.DesignA population-based analysis with linked register data.SettingFinland.Population56 963 patients with diabetes initiating statin use from 2005 to 2008.Main outcome measuresWe determined the proportions of real-world patients who fulfilled the eligibility criteria for HPS and CARDS trials and assessed the cardiovascular disease (CVD) event rates, assumed to reflect the background CVD risk, for those eligible and ineligible. We used descriptive statistics to identify the patient characteristics, lipid-lowering interventions and adherence to statin therapy.ResultsOf the real-world patients, 57% (N=32 582) fulfilled the eligibility criteria for HPS (DM) and 49% (N=20 499) of those without CVD for CARDS. The patients ineligible for HPS (DM) had a higher cumulative risk for CVD events than those eligible, whereas regarding CARDS the cumulative risks were of similar magnitude. The overall CVD event rates seemed to be comparable to those in the reviewed trials. Both trials were under-representative of women and users of antihypertensive agents and metformin. 27% and 29% of real-world patients had an initial statin dose corresponding to <20 mg of simvastatin. The proportions of patients who were deemed adherent were 57% in the real world and 85% in both trials.ConclusionsOnly half of the real-world patients would have qualified for the HPS (DM) and CARDS, limiting their representativeness for clinical practice. Women and users of antihypertensive agents and metformin were under-represented in both trials. These deviations reflect the changes in diabetes treatment over the years and are not expected to modify the average treatment effects of statins on CVD. Prescribing of lower statin doses in clinical practice than used in the trials and lower adherence may, however, attenuate the benefits in the real world.

Sex Differences in the Cardiovascular Consequences of Diabetes Mellitus

“…200,[202][203][204] Fewer women are represented in the combined data sets evaluating primary and secondary interventions with statins. 205,206 Despite that and given some conflicts in the data as to whether the impact of the effect is the same, expert opinion, supported by evidence, indicates that statins effectively lower cardiovascular risk for both women and men. Statins should be used in subjects with moderate or high CVD risk according to both new December 22/29, 2015…”

Long-term treatment adherence to the proprotein convertase subtilisin/kexin type 9 inhibitor alirocumab in 6 ODYSSEY Phase III clinical studies with treatment duration of 1 to 2 years

“…13 An average statin adherence rate of 85% was also demonstrated over a 5-year period in patients with diabetes from the large, randomized controlled Heart Protection Study. 11 In contrast, based on data from the Finnish FinDM database, the average adherence rate to statins over w3 years in patients with type II diabetes in the realworld setting was reported to be 57%. 11 Similarly, in a retrospective cohort study using the Saskatchewan Drug Plan and Extended Benefits database in Canada, adherence to statins was 52% in the first year and 44% by the third year.…”

“…11 In contrast, based on data from the Finnish FinDM database, the average adherence rate to statins over w3 years in patients with type II diabetes in the realworld setting was reported to be 57%. 11 Similarly, in a retrospective cohort study using the Saskatchewan Drug Plan and Extended Benefits database in Canada, adherence to statins was 52% in the first year and 44% by the third year. 39 Real-world data on adherence to ezetimibe capsules are limited; however, 1 retrospective study investigating oral LLTs, including the combination of ezetimibe and simvastatin, in a managed care setting demonstrated that mean proportion of days covered fell below the threshold for adherence (80%) even within the first 3 months of therapy.…”

“…Indeed, adherence to statins reported in clinical trials is greater than that observed in real-world settings (78%-90% vs 44%-57%, respectively). 11,12 In the Collaborative Atorvastatin Diabetes Study, in which patients with type II diabetes but no history of CVD were randomized to receive atorvastatin or placebo, 90% of patients allocated to the atorvastatin group were taking atorvastatin (and/or another statin) after 1 year, and 87% were taking atorvastatin (and/or another statin) at 2 years (85% of patients on average were taking atorvastatin and/or another statin over a 4year period). 12 In a cluster randomized sub-study of the Atorvastatin in Factorial with Omega EE90 Risk Reduction in Diabetes trial, adherence to atorvastatin over 1 year was w79%.…”

“…[3][4][5] Nonadherence to statin therapy is also relatively common, particularly in real-world settings where, compared with clinical trials, patients may be followed less rigorously. 2,[6][7][8][9][10][11] In clinical trials, adherence to statins has been reported to be 79% to 90% at 1 year and 78% at 4 years. 12,13 In contrast, in a cohort study conducted using 4 separate population-based administrative data sources, 2-year adherence rates with statin therapy were only 40.1% in patients with acute coronary syndromes, 36.1% in patients with coronary artery disease, and 25.4% in the primary prevention setting.…”